Aims We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. Methods and results We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [−0.12 (−0.22; −0.07)] than patients without new brain infarcts [0.07 (−0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. Conclusion In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844 Key question The incidence of clinically overt and silent brain infarcts, white matter lesions, and microbleeds, and their impact on cognition in atrial fibrillation (AF) patients are not known. Key finding Over 2 years of follow-up, 5.5% of AF patients developed new brain infarcts, with the majority of them being clinically silent and occurring in anticoagulated patients. New clinically overt and silent brain infarcts were similarly associated with cognitive decline. Take-home message In a contemporary cohort of AF patients, new brain infarcts are frequent despite a high anticoagulation rate. Our data suggest that anticoagulation alone may not be sufficient to prevent brain damage and cognitive decline in all AF patients.

Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-AF Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA2DS2-VASc score (congestive heart failure, hypertension, age 65-74 or ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1,379 atrial fibrillation patients (mean age 72 years, 27% female). Ischemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal Cognitive Assessment, Trail Making Test, Semantic Verbal Fluency and Digit Symbol Substitution Test, which were summarized using principal component analysis. Results were analyzed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA2DS2-VASc score, with an average 19.2% (95% confidence interval [17.2%, 21.3%]) higher neurofilament per unit CHA2DS2-VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age (32.5% [27.2%, 38%] neurofilament increase per 10 years), diabetes mellitus, heart failure and peripheral artery disease (26.8% [16.8%, 37.6%], 15.7% [8.1%, 23.9%] and 19.5% [6.8%, 33.7%] higher neurofilament, respectively). Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts (4.3% [1.8%, 6.8%] and 5.5% [2.5%, 8.7%] neurofilament increase per unit increase in log-volume of the respective lesion), as well as normalized brain volume (4.9% [1.7%, 8.1%] higher neurofilament per 100 cm3 smaller brain volume). Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function.

AimsThis study aimed to analyse health related quality of life (HRQoL) for patients with different atrial fibrillation (AF) types and to identify patient characteristics, symptoms and comorbidities that influence HRQoL.MethodsWe used baseline data from the Swiss Atrial Fibrillation (Swiss-AF) study, a prospective multicentre observational cohort study conducted in 13 clinical centres in Switzerland. Between April 2014 and August 2017, 2415 AF patients were recruited. Patients were included in this analysis if they had baseline HRQoL data as assessed with EQ-5D-based utilities and visual analogue scale (VAS) scores. Patient characteristics and HRQoL were described stratified by AF type. The impact of symptoms, comorbidities and socio-economic factors on HRQoL was analysed using multivariable regression analysis.ResultsBased on 2412 patients with available baseline HRQoL data, the lowest unadjusted mean HRQoL was found in patients with permanent AF regardless of whether measured with utilities (paroxysmal: 0.83, persistent: 0.84, permanent: 0.80, p<0.001) or VAS score (paroxysmal: 73.6, persistent: 72.8, permanent: 69.2, p<0.001). In multivariable analysis of utilities and VAS scores, higher European Heart Rhythm Association (EHRA) score, recurrent falls and several comorbidities showed a strong negative impact on HRQoL while AF type was no longer associated with HRQoL.ConclusionsMultiple factors turned out to influence HRQoL in AF patients. After controlling for several comorbidities, the EHRA score was one of the strongest predictors independent of AF type. The results may be valuable for better patient assessment and provide a reference point for further QoL and health economic analyses in AF populations.

Background Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is considered as risk factor for the development of mild cognitive impairment (MCI) and dementia. However, dynamics of cognitive functions are subtle, and neurocognitive assessments largely differ in detecting these changes. We aimed to develop and evaluate a score which represents the common aspects of the cognitive functions measured by validated tests (i.e., "general cognitive construct"), while reducing overlap between tests and be more sensitive to identify changes in overall cognitive functioning. Methods We developed the CoCo (cognitive construct) score to reflect the cognitive performance obtained by all items of four neurocognitive assessments (Montreal Cognitive Assessment (MoCA); Trail Making Test; Semantic Fluency, animals; Digital Symbol Substitution Test). The sample comprised 2,415 AF patients from the Swiss Atrial Fibrillation Cohort Study